INHIBITION OF MULTIPLICATION 207 



the chorioallantoic membrane in vitro is probably somewhat less than 4 hours 

 (Tamm and Tyrrell, 1954). The compound is most effective during about the 

 first half of the latent period, and has little or no inhibitory activity during 

 the last half of the period. Its inhibitory effect on the production of 

 the soluble antigen is restricted to about the first eighth of the latent 

 period. 



DEB does not inactivate influenza viruses in vitro, has no effect on virus- 

 erythrocyte interaction, does not interfere with adsorption of the virus by 

 host tissue, and does not affect the release of new virus particles from the 

 chorioallantoic membrane (Tamm et al., 1954). At concentrations causing 

 99 % inhibition of influenza B virus multiplication it does not affect the 

 oxygen uptake of the membrane nor does it diminish tissue proliferation in 

 roller tube culture. At higher concentrations it retards cell proliferation but 

 this effect is reversed on removal of the compound (Tamm et al., 1954). When 

 the concentration is increased sufficiently, reduction in oxygen uptake and 

 both microscopic and macroscopic damage of the membrane occur (Tamm, 

 1956b). 



Because the inhibition caused by DRB is produced only during the first 

 half of the latent period and because it does not affect any other step in the 

 process of infection, it seemed probable that it acts by interfering with 

 metabolic processes involving ribofuranosides and that it might affect 

 nucleic acid metabolism (Tamm et al., 1954). This hypothesis was suggested 

 by the close chemical relationships between a-ribazole, a moiety of vitamin 

 Bi 2 , adenosine, a constituent of ribonucleic acid, and DRB (Tamm et al., 

 1954). Recently Tamm (1957) demonstrated that DRB does in fact interfere 

 with the incorporation of adenosine-8-C 14 into ribonucleic acid (RNA) of the 

 chorioallantoic membrane. Moreover, Allfrey et al. (1957) showed that DRB 

 greatly reduces the incorporation of orotic acid-C 14 into nuclear RNA and 

 seems to block the synthesis of RNA within the nucleus, no matter when it is 

 added to the medium. The finding that DRB does not inhibit multiplication 

 after the latent period suggests that inhibition of host cell RNA synthesis 

 at this late stage is of no consequence in virus reproduction (Tamm, 

 1958). 



Studies of the incorporation of C 14 -L-alanine into the protein of the chorio- 

 allantoic membrane indicate that DRB has little if any effect on protein 

 synthesis (Tamm, 1957). If nucleic acid precursors of influenza virus are 

 synthesized in the virus-infected cell before protein precursors, as appears to 

 occur with bacterial viruses (Hershey and Melechen, 1957), it may not be 

 surprising that DRB inhibits multiplication only during the first part of the 

 latent period (Tamm and Tyrrell, 1954). 



The high inhibitory activity of /3-D-ribofuranosides of benzimidazole, 

 relative to influenza virus multiplication, depends not only on the number of 



